1885-14-9Relevant articles and documents
Rational design and screening study of novel lead compound based on acetohydroxyacid synthase structure
Jin, Jingnan,Qi, Xiaojuan,Yao, Dandan,Mao, Bangqiang,Li, Jianhong,Zhang, Qingye,Chen, Changshui
, p. 316 - 324 (2014)
Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long-term excessive use of commercial AHAS-inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit-10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor-/ligand-binding mode. Three novel 5-substituted benzyl-1,3,4-thiadiazol-2-carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54-32.05 mg/L range, and the inhibition rates were increased by 30-50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides. Lead compound with IC50 value of 47.41 mg/L was screened out based on AHAS target. Optimization and syntheses of lead compound were performed, and the inhibition rates of the synthesized compound increased by 30-50%. The possible inhibitory mechanisms were analyzed by molecular docking.
Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents
Park, Eun Beul,Kim, Kwang Jong,Jeong, Hui Rak,Lee, Jae Kyun,Kim, Hyoung Ja,Lee, Hwi Ho,Lim, Ji Woong,Shin, Ji-Sun,Koeberle, Andreas,Werz, Oliver,Lee, Kyung-Tae,Lee, Jae Yeol
, p. 5193 - 5197 (2016)
In our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE2levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a–7c) and the other regioisomer corresponds to a thermodynamic product (8a–8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2assay studies showed that the kinetic product (7a and 7b; IC50= 0.69 and 0.55 μM against PGE2) is generally more potent than the thermodynamic product (8a and 8b; IC50= >10 and 0.79 μM against PGE2). A molecular docking study also exhibited that the kinetic product (7a) has a higher MolDock Score (?147.4) than that of 8a (?142.4), which is consistent with the PGE2assay results. A new potent phenylsulfonyl hydrazide (7d; IC50= 0.06 μM against PGE2) without affecting COX-1 and COX-2 enzyme activities was identified based on these overall results.
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
supporting information, p. 12324 - 12332 (2020/08/06)
Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.
Synthetic approaches to a challenging and unusual structure—an amino-pyrrolidine guanine core
Rippel, Rafael,Pinheiro, Luís,Lopes, Mónica,Louren?o, Ana,Ferreira, Luísa M.,Branco, Paula S.
, (2020/02/25)
The synthesis of an unreported 2-aminopyrrolidine-1-carboxamidine unit is here described for the first time. This unusual and promising structure was attained through the oxidative decarboxylation of amino acids using the pair of reagents, silver(I)/peroxydisulfate (Ag(I)/S2O82?) followed by intermolecular (in the case of L-proline derivative) and intramolecular trapping (in the case of acyl L-arginine) by N-nucleophiles. The L-proline approach has a broader scope for the synthesis of 2-aminopyrrolidine-1-carboxamidine derivatives, whereas the intramolecular cyclization afforded by the L-acylarginines, when applied, results in higher yields. The former allowed the first synthesis of cernumidine, a natural alkaloid isolated in 2011 from Solanum cernuum Vell, as its racemic form.
PROCESS FOR PRODUCING CHLOROFORMATE COMPOUND
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Paragraph 0079; 0087, (2019/06/20)
The present invention provides a method for safely producing a large amount of chloroformate compound with high yield. The chloroformate compound can be produced by mixing and reacting a solution of triphosgene, an amine and an alcohol compound in a flow reactor. The chloroformate compound can also be produced by mixing and reacting a solution of triphosgene with a solution comprising an amine and an alcohol compound in a flow reactor. The amine is preferably tributylamine, and preferably used in an amount of 0.8 to 3 equivalents relative to an amount of the alcohol compound.
Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as new antitubercular agents with potent in vitro and in vivo efficacy
Cheng, Ya-Juan,Liu, Zhi-Yong,Liang, Hua-Ju,Fang, Cui-Ting,Zhang, Niu-Niu,Zhang, Tian-Yu,Yan, Ming
, (2019/06/07)
A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.
Visible-Light-Induced Intramolecular C(sp2)-H Amination and Aziridination of Azidoformates via a Triplet Nitrene Pathway
Zhang, Yipin,Dong, Xunqing,Wu, Yanan,Li, Guigen,Lu, Hongjian
supporting information, p. 4838 - 4842 (2018/08/24)
Catalytic intramolecular C-H amination and aziridination reactions of o-allylphenyl azidoformates have been achieved under visible-light irradiation, providing a mild, clean, and efficient method for the synthesis of useful benzoxazolones and [5.1.0] bicyclic aziridines. Mechanistic studies suggest that a triplet nitrene acts as the reactive intermediate. The chemoselectivity of the reaction, with alkyl olefin aziridination ? electron deficient olefin aziridination ≈ C(sp2)-H amination ? C(sp3)-H amination was observed, which may be instructive in the development of an understanding of visible-light-induced triplet nitrene transformation reactions.
Bis-Acetyl Carbazole: A Photoremovable Protecting Group for Sequential Release of Two Different Functional Groups and Its Application in Therapeutic Release
Venkatesh, Yarra,Nandi, Surajit,Shee, Maniklal,Saha, Biswajit,Anoop, Anakuthil,Pradeep Singh
, p. 6121 - 6130 (2017/11/15)
In this paper, we present fluorescent photoremovable protecting groups (FPRPG) based on bis-acetyl carbazole for the release of two different functional groups such as carboxylic acids, alcohols, thiols, and amines in a sequential fashion. Dual-arm caged bis-acetyl carbazoles with different combinations of two unlike functional groups were synthesized. Photophysical studies showed that caged bis-acetyl carbazoles are blue fluorescent and their emission properties are sensitive to the environment. Sequential photorelease of two different functional groups by bis-acetyl carbazole was analyzed by HPLC, UV and emission spectroscopy. The mechanism of the dual release by bis-acetyl carbazole was investigated and supported by TD-DFT calculations. To demonstrate the applicability of the dual release ability of bis-acetyl carbazole FPRPG, we synthesized a drug delivery system (DDS) in which one arm of bis-acetyl carbazole is linked to the carboxylic functional group of chlorambucil (CBL) and the other arm is attached to the hydroxyl group of ferulic acid ethyl ester (FAEE). In vitro studies showed that our DDS presents excellent properties such as photoregulated dual drug delivery, cellular uptake, and biocompatibility.
Synthetic method for preparing pure phenyl chloroformate with two-step method
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Paragraph 0015-0019; 0022-0024, (2018/02/04)
The invention provides a synthetic method for preparing pure phenyl chloroformate with a two-step method. The method comprises main steps as follows: (1) phenol in a molten state and a small quantity of a catalyst DMF (dimethyl formamide) are added to a flask, stirring is started, phosgene is introduced at a certain temperature, activated carbon is added after complete reaction, nitrogen is introduced to a reaction solution, and crude phenyl chloroformate is obtained after the reaction ends; (2) obtained crude phenyl chloroformate is subjected to reduced pressure distillation, and pure phenyl chloroformate is obtained. Compared with the prior art, the method has the advantages as follows: aftertreatment is simple, use of large quantities of acid-binding agents and solvents is effectively avoided, no industrial waste water is produced, the cost is relatively low, the method is suitable for industrial production, and meanwhile, possible harm to the phosgene can be reduced through improvement of equipment.
